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Powerful gene-editing tool can eliminate HIV infection in mice

Scientists have made an early but important development in the fight against HIV.

For the first time, a team of researchers has shown that they can remove HIV type 1 (HIV-1) from infected mouse cells using a powerful gene-editing tool. By removing DNA of the deadly virus in rodents, they also stopped the virus from replicating.

While a permanent cure for HIV in humans remains a ways off, the new study is a major step toward achieving that goal, according to scientists at the University of Pittsburgh and Temple University's Lewis Katz School of Medicine.

The journal Molecular Therapy published the team's findings on Wednesday.

"The next stage would be to repeat the study in primates," Kamil Khalili, a co-author of the study who chairs Temple's neuroscience department, said in a press release. "Our eventual goal is a clinical trial in human patients."

Image: molecular therapy

For their study, researchers used CRISPR/Cas9, a tool that enables scientists to edit parts of the genome — our full genetic material — by removing, adding, or altering sections of the DNA sequence.

They did this by injecting live mice with a virus-bacteria combo that performed the gene editing within their tissues.

The new work builds on an earlier proof-of-concept study that involved genetically modified, or "transgenic," mice and rats. After incorporating the DNA of HIV-1 into the genome of every tissue of the animals' bodies, the team found it could delete targeted fragments of HIV-1 from the genome in most tissues.

"Our new study is more comprehensive," Wenhui Hu, a co-author and associate professor of pathology at Temple, said in the news release. He noted the team has "improved the efficiency" of their approach this time by adding two mouse models.

In the first model, researchers again used transgenic mice to confirm their previous findings. The team genetically inactivated HIV-1 in the mice, thus reducing the RNA expression of viral genes by 60 to 95 percent. That means they stopped RNA, which act as a genetic messenger, from relaying the toxic information.

A scientist in China worker performs an HIV test at a lab in Shanghai.

Image: china photos/Getty Images

For the two other models, scientists studied mice with actively replicating HIV infections and mice with latent infections that lie dormant within the cells.

Mice with active infections had EcoHIV, the mouse equivalent of human HIV-1. Using CRISPR/Cas9, researchers were able to block replication of the virus and show they could potentially prevent systemic infection — marking the first evidence that this method can eradicate the virus.

For the latent infections, the team studied "humanized" mice that had been engrafted with human immune cells, including T cells. (People with HIV/AIDS have a devastatingly low number of a particular type of T cell.) The mice were also infected with latent HIV-1.

After just one CRISPR/Cas9 treatment, researchers successfully removed viral fragments of the infected human cells embedded in mouse tissues and organs.

Human trials might take years to conduct, but Khalili said primates are an ideal next step after rodents. Primates are "a more suitable model where HIV infection induces disease, in order to further demonstrate elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells," he said.

They used the tool in three different animal models. First, in genetically modified "transgenic" mice, they inactivated the HIV-1 virus by reducing the RNA expression of viral genes. That means they stopped RNA — which act as messengers — from relaying the viral information.

a more suitable animal model where HIV infection induces disease, in order to further demonstrate elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells,” Dr. Khalili said. “Our eventual goal is a clinical trial in human patients.”

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